Abstract: This document features methods and materials involved in predicting responsiveness of a mammal (e.g., human) having cancer (e.g., glioblastoma multiforme) to treatment with chemotherapy (e.g., temozolomide). For example, methods and materials for using the methylation status at one or more CpG methylation sites (e.g., CpG 89) in O6-methylguanine methyl-transferase nucleic acid to determine whether or not a mammal having cancer is responsive to treatment with chemotherapy (e.g., temozolomide) are provided.